Cardiovascular morphogenesis and pathogenesis involve biochemical and morphological changes in the extracellular matrix and we propose to study four separate but related areas which bear on the dynamic role of the connective tissue matrix in the cardiovascular system: 1) Vascular scar maturation - a morphological and biochemical characterization of human atherosclerotic lesions as they change with age; 2) Valvulogenesis and valvulopathy - a morphological and biochemical study of the development of normal valvular tissue and its biochemical and ultrastructural change during calcific scarring and floppy degeneration; 3) Basement membranes as receptors with high capacity and low specificity - a series of studies directed toward binding by basement membranes of biologically active substances of interest in cardiovascular physiology; and 4) Matrix interactions during thrombocyte maturation - an examination of thrombocyte life span from megakaryocyte maturation and platelet release in the bone marrow to the interactions of platelets with collagens in the peripheral vascular system. Production of collagen type-specific antibodies for use in all the above studies will be undertaken.